Immunoglobulin G is known to enhance the rate and extent of alternative complement pathway activation on a variety of targets, and to facilitate complement-mediated destruction of some bacteria and virus-infected cells. We have shown that C3b residues covalently deposited on IgG are relatively protected from the actions of serum factors H and I, and hence have enhanced capacity to sustain alternative pathway activation. Human CR1 can overcome this protection, but binds weakly unless C3b is presented in a multivalent form. We have demonstrated that C3b-IgG complexes are highly efficient sensitizers of E. coli for complement-mediated killing and have suggested, on a statistical basis, the C3b bound to IgG may be the major C3b species mediating serum-killing of this organism. Future directions include studies of the mechanisms of enhanced complement lysis of C3b-IgG bearing targets, attempts to localize the C3b acceptor site on human IgG, and investigation of the opsonic capacity of C3b-IgG complexes.